A Phase II Study of Durvalumab and Tremelimumab in Patients With Advanced Rare Tumours
A Phase II Study of Durvalumab and Tremelimumab in Patients With Advanced Rare Tumours
The standard or usual treatment for this disease may be chemotherapy or other types of treatment to slow the spread of the disease and relieve some symptoms of this cancer.
Durvalumab is a new type of drug for many types of cancer. Laboratory tests show that it works by allowing the immune system to detect cancer and stimulate the immune response. This may help to slow down the growth of cancer or may cause cancer cells to die. Durvalumab has been shown to shrink tumours in animals and has been studied in 5000 people and seems promising but it is not clear if it can offer better results than standard treatment alone.
Tremelimumab is a new type of drug for various types of cancers. It works in a similar way to durvalumab and may improve the effect of durvalumab. This may also help slow the growth of the cancer cells or may cause cancer cells to die. Tremelimumab has been shown to shrink tumours in animals and has been studied in 1500 people and seems promising but it is not clear if it can offer better results than standard treatment alone when used with durvalumab
Combinations of durvalumab and tremelimumab have also been studied and when combined have been shown to increase tumour shrinkage in animals compared to either drug alone. While the combination has been studied in 250 people, it is not clear if it can offer better results than standard treatment.
Inclusion Criteria:
Patients must have histologically and/or cytologically confirmed cancer that is advanced / metastatic / recurrent or unresectable and for which no curative therapy exists as follows:
All patients must have a tumour tissue from their primary or metastatic tumour available
Presence of clinically and/or radiologically documented disease. All radiology studies must be performed within 28 days prior to registration (within 35 days if negative).
All patients must have at least one measurable lesion as defined by RECIST 1.1 that has not been the site of the protocol mandated biopsy. The criteria for defining measurable disease are as follows:
CT scan (with slice thickness of 5 mm) ≥ 10 mm --> longest diameter Lymph nodes by CT scan ≥ 15 mm --> measured in short axis
Cytotoxic Chemotherapy:
Patients may have received prior chemotherapy - no limit on number of prior regimens.
Other Systemic Therapy:
Patients may have received other prior therapies including, angiogenesis inhibitors, PARP inhibitors or signal transduction inhibitors (tyrosine kinase inhibitors). Prior therapy with PD-1/PD-L1 or CTLA-4 inhibitors is not allowed.
Patients must have recovered from all reversible toxicity related to prior chemotherapy or systemic therapy (unless grade 1, irreversible, or considered by investigator as not clinically significant) and have adequate washout as follows:
Longest of one of the following:
Radiation:
Prior external beam radiation is permitted provided a minimum of 28 days (4 weeks) have elapsed between the last dose of radiation and date of registration. Exceptions may be made for low-dose, non-myelosuppressive radiotherapy after consultation with CCTG senior investigator. Concurrent radiotherapy is not permitted. Patients planned for concurrent chemotherapy-radiation are not eligible.
Surgery:
Previous surgery is permitted provided that a minimum of 28 days (4 weeks) have elapsed between any major surgery and date of registration, and that wound healing has occurred.
Absolute neutrophils ≥ 1.5 x 10^9/L Platelets ≥ 100 x 10^9/L Hemoglobin ≥ 90 g/L Bilirubin ≤ 1.5 x ULN (upper limit of normal)* AST and ALT ≤ 2.5 x ULN (if liver metastases are present, ≤ 5 x ULN) Serum creatinine < 1.25 x ULN or: Creatinine clearance ≥ 40 mLs/min
Exclusion Criteria:
Patients with a history of other malignancies, except: adequately treated non-melanoma skin cancer, curatively treated in-situ cancer of the cervix, or other cancers curatively treated with no evidence of disease for ≥ 5 years.
Active or prior documented autoimmune or inflammatory disorders including inflammatory bowel disease (e.g. colitis or Crohn's disease), diverticulitis with the exception of diverticulosis, celiac disease or other serious gastrointestinal chronic conditions associated with diarrhea), systemic lupus erythematosus, Sarcoidosis syndrome, or Wegener syndrome (granulomatosis with polyangiitis), rheumatoid arthritis, hypophysitis, uveitis, etc., within the past 3 years prior to the start of treatment. The following are exceptions to this criterion:
History of primary immunodeficiency, history of allogenic organ transplant that requires therapeutic immunosuppression and the use of immunosuppressive agents within 28 days of registration.
Live attenuated vaccination administered within 30 days prior to registration.
History of hypersensitivity to durvalumab or tremelimumab or any excipient. Any previous treatment with a PD1 or PD-L1 inhibitor, including durvalumab or an anti-CTLA4, including tremelimumab.
Patients who have experienced untreated and/or uncontrolled cardiovascular conditions and/or have symptomatic cardiac dysfunction (unstable angina, congestive heart failure, myocardial infarction within the previous year or cardiac ventricular arrhythmias requiring medication, history of 2nd or 3rd degree atrioventricular conduction defects). Patients with a significant cardiac history, even if controlled, should have a LVEF ≥ 50%.
Untreated symptomatic brain metastases or brain metastases in whom radiation or surgery is indicated.
Concurrent treatment with other investigational drugs or anti-cancer therapy.
Patients with serious illnesses or medical conditions which would not permit the patient to be managed according to the protocol (incl corticosteroid administration), or would put the patient at risk. This includes but is not limited to:
Pregnant or lactating women.